The tanning response is characterized clinically by the formation of brown color in the skin that is exposed to ultraviolet radiation and histologically by an increase in the epidermal melanin content. This increase in pigmentation is the outcome of two main events: the synthesis of melanin by melanocytes and the donation of melanin in melanosomes to the surrounding keratinocytes. In mammalian cells the rate of melanin production is determined by the intracellular enzyme Tyrosinase and two related proteins TRP-1 and TRP-2 (Dopachrome tautomerase). Tyrosinase is a copper containing oxidase that catalyzes three different reactions in the melanogenesis pathway. The first two reactions result in the conversion of tyrosine to dopa and in the subsequent conversion of dopa to dopaquinone. The third reaction occurs at the distal step in the pathway, in which 5,6-dihydroxyindole is oxidized to indolequinone. An increase in tyrosinase activity provides an increase in tanning which occurs along the melanin synthetic pathway. Tyrosinase activity increases when the skin is exposed to sunlight, thus triggering the cascade which causes the darkening of the skin. Despite an understanding of the enzymatic processes underlying melanin production, the precise mechanism by which the sun initiates this activity is still unknown.
The desire for a deep tan has generated a proliferation of products claiming to enhance the tanning process. Most of these products contain tyrosine, tyrosine derivatives and /or amino acid blends. Despite the claims of the producers, a number of independent studies have demonstrated that these products, when used according to package insert instructions, showed a lack of efficacy in tan acceleration.
Theophylline is a potent stimulator of melanogenesis in melanoma cell lines. This activity has been attributed to inhibition of mammalian phosphodiesterase which further causes an elevation in cAMP levels. cAMP is believed to increase the activity of tyrosinase. Consequently, it has also been postulated that melanin production can be increased by increasing cAMP levels. In support of this theory, a hormone, .alpha.-MSH, has been shown to increase melanin production through activation of adenylate cyclase, thereby increasing cAMP levels. Although this hormone can stimulate the tanning process, .alpha.-MSH is a potent neuropeptide and is unsuitable for use in topical creams.
What is needed in the art are new compositions which modulate melanin production and thereby lighten the skin or hair or promote tanning for both pharmaceutical and cosmetic purposes. The compositions should provide the modulation of melanin production by acting on specific receptors or enzymes in the melanin cascade. Surprisingly, the present invention provides such methods and compositions.